P-0176 - The levels of methionine determined byamino acid profiling correlate with thedegree of methylation in colon cancertissues

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Colon Cancer
Translational Research
Presenter Yuji Takayama
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors Y. Takayama1, Y. Muto1, K. Suzuki1, T. Kato2, K. Ichida3, T. Fukui3, M. Saito1, S. Tsujinaka1, H. Kamiyama4, J. Sasaki1, H. Horie3, K. Kiyozaki1, T. Rikiyama1
  • 1Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama-shi/JP
  • 2Jichi Medical Center, Saitama/JP
  • 3Saitama Medical Center, Jichi Medical University, Saitama/JP
  • 4Chichibu City Hospital, Chichibu-shi/JP

Abstract

Introduction

Methionine is an important amino acid as a supply of methyl group for epigenetic modifications of DNA and histone proteins, leading to methylation or demethylation. Decreased level of methylation (demethylation) aggravates chromosomal instability in microsatellite stable cancer (MSS). Our previous reports showed that decreased level of methylation was seen not only in cancer but surrounding normal tissues in some colorectal and gastric cancer patients. Further, decreased levels of methylation were enhanced in normal tissues from patients with multiple tumors. Recent paper reported that serum levels of methionine determined by amino acid profiling using AminoIndex Technology enable to calculate the risks for colon cancer. In this study, we elucidate levels of methionine and their relationship to demethylation levels in colon cancer tissues.

Methods

Thirty-nine colon cancer patients were recruited in this study, including 8 patients with microsatellite unstable cancer (MSI) and 31 with MSS. The relative demethylation levels (RDLs) of repetitive sequences such as satellite alpha (SAT-A), were quantified by real-time methylation-specific polymerase chain reaction using bisulfite-treated genomic DNA. Centromere region consists of these SAT-A sequences, demethylation of which leads to chromosomal instability. The level of methionine was determined by amino acid profiling using AminoIndex Technology.

Results

The SAT-A RDL varied from 0.158 to 3.316 (mean, 0.715). The levels of methionine varied from 0 to 1511 (mean, 147.7). Regression analysis showed significant correlation between SAT-A RDL and levels of methionine (p = 0.0018). When comparing between tumors with low SAT-A RDL and high, tumors with high (much demethylation, n = 20) likely showed high levels of methionine than tumors with low (low demethylation, n = 19) (218.7 in high vs. 80.7 in low, p = 0.182) but no significant difference was seen. Tumors with MSS likely showed high levels of methionine than those with MSI (166.1 in MSS vs. 94.6 in MSI, p = 0.581). Distribution of levels of SAT-A RDL revealed that tumors with RDL> 0.715 of the mean value (H-RDL: more demethylation, n = 7) exhibited remarked levels of methionine than tumors with RDL< 0.715 (L-RDL: less demethylation, n = 32) (418.3 vs. 93.1, p= 0.0131).

Conclusion

Colon cancer patients harboring tumors with more demethylation showed remarked levels of methionine determined by amino acid profiling in tumor tissues, suggesting that these patients could be detected by amino acid profiling in blood using AminoIndex Technology.